Glaucoma is a slow and irreversible neuro-degenerative disease whose onset is usually not detected by the patient. Diagnosis may be based on a combination of variables (Quigley, New England Journal of Medicine: 328:1097–1106 (1993); Sommer. Eye: 10:295–30 (1996)) but the most dependable single index is probably the identification of a characteristic pattern of visual field defects. However these defects may only appear after a substantial amount of retinal damage has occurred (Pederson & Andserson, Arch Ophthalmol. 98:490–495 (1980); Quigley et al., Arch Ophthalmol 100:135–146 (1982); Sommer et al., Arch Ophthalmol: 97:1444–1448 (1979), Sommer et al., Arch Ophthalmol: 109:77–83 (1991)). There is a widely accepted need therefore for methods which may be used to detect glaucomatous damage. Ideally, such a test would have high sensitivity and specificity and be quickly and cheaply administered to large numbers of the normal population, especially those most likely to be at risk of the disease, such as the elderly and those with a family history of glaucoma.
A variety of scanning laser ophthalmoscopes are known, such as shown in U.S. Pat. No. 4,765,730; U.S. Pat. No. 4,764,006 and U.S. Pat. No. 4,768,873 (all of which are incorporated herein by reference). For example, the Heidelberg Retina Tomograph (HRT) is a confocal laser scanning microscope which may be used for acquisition and analysis of three-dimensional images of the posterior segment of the eye (the fundus). In operation, to acquire digital confocal images, a laser beam is focused on the retina. Oscillating mirrors provide periodic deflection of the laser beam to facilitate sequential scanning of a two-dimensional field of the retina, in which the reflectance at a number of points is measured. To obtain confocal images, light reflected at the adjusted focal plane is measured, to the exclusion of out-of-focus light, to provide a two-dimensional confocal image of an optical section of the retina at the focal plane. A series of optical section images may be acquired, with different focal planes, resulting in a layer-by-layer three-dimensional image. The distribution of reflected light in the three-dimensional image may be assessed to compute the retinal surface height at each point. The matrix of height measurements may be visualized as a topographic image which reflects the three-dimensional retinal surface. In some commercial embodiments, the Heidelberg Retina Tomograph uses a diode laser with a wavelength of 670 nm, and may be used to acquire a three-dimensional image as 32 consecutive and equidistant optical section images, each consisting of 256×256 picture elements. The size of the field of view may be set to 10°×10°, 15°×15°, or 20°×20°. Topographic images may be computed from the acquired three-dimensional images, in which the topographic image consists of 256×256 individual height measurements which are scaled for the individual eye examined.
The Heidelberg Retina Tomograph has been used to obtain three-dimensional images of the surface topography of the optic nerve head (ONH) (Weinreb et al., Int Ophthalmol: 13:25–27 (1989); Kruse et al., Ophthalmology: 96:1320–1324 (1989); Dreher et al., Am J Ophthalmol. 111:221–229 (1991); Cioffi et al., Ophthalmology; 100:57–62 (1993); Mikelberg et al., J. Glaucoma. 2:101–103 (1993); Lusky et al., J. Glaucoma. 2:104–109 (1993); Rohrschneider et al., Graefes Arch Clin Exp Ophthalmol. 231:457–464 (1993), Rohrschneider et al. Ophthalmology. 101:1044–1049 (1994); Bartz-Schmidt et al., Ger J Ophthalmol 3:400–405 (1994); Chauhan et al., Am J Ophthalmol. 118:9–15 (1994); Janknecht and Funk, Br J Ophthalmol. 78:760–768 (1994); Orgul et al., Arch Ophthalmol. 114:161–164 (1996)). In moderate and advanced cases of glaucoma this damage leads to anatomical changes in the morphology of the optic disc region, including enlargement of the depression on the centre of the disc, known as the cup. A number of studies has shown that morphological indices calculated from images of the ONH differ significantly between normal eyes and eyes with glaucomatous visual field defects (Burk et al, Kin Monatsbl Augenheilkd. 198:522–529 (1991); Brigatti & Caprioli, Arch Ophthalmol. 113:1191–1194 (1995); Mikelberg et al., J Glaucoma. 4:242–247 (1995); Weinreb et al., Am J Ophthalmol. 120:732–738 (1995); Brigatti et al., Am J Ophthalmol. 121:511–521 (1996); Uchida et al., Invest Ophthalmol Vis Sci. 37:2393 –2401 (1996); Hatch et al., Br J Ophthalmol. 81:871–876 (1997); lester et al., J Glaucoma. 6:78–82 (1997a); lester et al., Can J Ophthalmol.; 32:382–388 (1997b); lester et al., Ophthalmology 104:545–548 (1997c); Anton et al., Am J Ophthalmol. 125:436–446 (1998); Bathija et al., J Glaucoma 7:121–127 (1998); Wollstein et al., Ophthalmology. 105:1557–1563 (1998)). Parameters calculated from combinations of these indices can be used to diagnose the presence of glaucomatous field loss, within the populations from which normative values were obtained, with sensitivities and specificities that are typically in the range of 80–90%.0
These methods typically rely on shape parameters which are calculated by software following an initial stage in which a technician or clinician uses a computer input device such as a mouse to manually outline the edge of the optic disc. This outlining process has been controversial because different observers do not always agree where the disc margins should be placed and this introduces an element of uncontrolled variability into the morphological analysis (Orgul et al., Graefes Arch Clin Exp Ophthalmol. 235:82–86 (1997)). Thus, while the art provides a method for interpretation of scanning laser ophthalmoscope 3-dimensional images of ONH surface topography, there is typically a manual component that introduces variability and requires the time and efforts of a skilled technician. There is therefore a need for image processing techniques that may be automated so that they do not require this kind of manual intervention.
Images of normal and glaucomatous optic nerve heads obtained with the scanning laser ophthalmoscope typically exhibit a central, roughly circular depression of variable width and depth (the cup), superimposed on a relatively smooth surface with a variable degree of curvature (the rim region). This curvature is almost always convex, and is caused by the layer of ganglion cell axons becoming, of geometrical necessity, increasingly thick as the axons converge towards the optic nerve.